In recent years, there have been aggressive attempts to search a molecule that exhibits a specific interaction with a particular molecule have been actively conducted using a technique based on specific intermolecular interactions. Against this background, a method of immobilizing a low-molecular compound like a pharmaceutical exhibiting noteworthy physiological activity onto an appropriate solid phase carrier, and searching a target, is drawing attention. Since target search research using this technique called affinity resin enables efficient identification of a target for a low-molecular compound exhibiting a physiological activity of interest, many investigations have been conducted and some specific achievements have been reported. As examples of these investigations, 1) the discovery of FKBP proteins, which bind to the immunosuppressant FK506 (FK506 binding proteins), by Professor Schreiber in 1989 (discovery of FKBP12 as a protein that binds to FK506 in cells; see “Nature, UK, Oct. 26, 1989, Vol. 341, pp. 758-760”), 2) the discovery of HDAC as a target protein for the anticancer agent Trapoxin (see “Science, USA, Apr. 19, 1996, Vol. 272, pp. 408-411”), and 3) the discovery of Ref-1 as a target protein for E3330 by Handa et al. (see “Nature Biotechnology, UK, August 2000, Vol. 18, No. 8, pp. 877-881”) are known well. In the area of diagnostic reagents, therapeutic efficacy increases if the presence of a lesion is non-invasively detectable as early after onset of disease as possible; therefore, for example, there are brisk research activities to identify a substance called a marker, such as a trace protein, which is specifically expressed in a particular cancer, in a collected patient blood and the like.
To date, however, in the above-described technique, the presence of non-specific proteins other than the protein involved in a specific intermolecular interaction with an immobilized ligand molecule has been problematic. The present inventors have already found that by allowing a hydrophilic spacer to interlie between a ligand and an affinity resin during the binding thereof, non-specific interactions between the immobilized ligand molecule and/or the affinity resin itself and molecules that are not specific for the ligand are reduced (Japanese Patent Application No. 2002-222226 (WO2004/025297)). However, focusing on the reduction of non-specific interactions, affinity resins having a highly hydrophilic solid phase carrier, like agarose-series affinity resins (for example, AffiGel), serve excellently as affinity resins. However, agarose-series resins are faulty in that they are not always suitable for research into a broad range of ligands because they cause irreversible denaturation due to the chemical characteristics of the constituents thereof in many systems in common use for synthesis. From the viewpoint of stability, methacrylate-series resins (for example, TOYOPEARL) are chemically stable and exhibit sufficient resistance to reactions in many organic solvents.
There has been a demand for the development of a resin having intermolecular non-specific interactions reduced to an extent comparable to that of agarose-series affinity resins, and possessing a stability comparable to that of methacrylate-series resins.
It is an object of the present invention to provide a resin capable of reducing intermolecular non-specific interactions, and possessing excellent stability, particularly an affinity resin.